Immune response in rabbits to virion and nonvirion antigens of the Flavivirus kunjin

Abstract

The nature of the antibodies formed in rabbits in response to the following Kunjin virus antigens was examined: infectious suckling mouse brain (SMB), purified virion or rapidly sedimenting hemagglutinin (RHA), slowly sedimenting hemagglutinin (SHA), and envelope fragments prepared from RHA disrupted by 0.1 or 0.2% sodium deoxycholate (DOC). The hemagglutination-inhibiting (HI) and neutralizing antibody responses to SMB, RHA, and large envelope fragments (0.1% DOC) were remarkably uniform, antibodies appearing at the same time, attaining similar HI titers (lowest to envelope), and being of similar avidity early and late in the respone. The 19S (immunoglobulin M) antibodies to all antigens were always relatively type-specific, whereas the 7S (immunoglobulin G) antibodies were always broadly cross-reactive in HI tests. These results confirm that the envelope antigen is the principal antigen involved in the stimulation of protective neutralizing antibodies and contains both type- and group-specific antigenic determinants. The results also establish that there is no significant advantage in using purified RHA or SHA either for immunization or as hemagglutinin antigens in attempts to obtain greater specificity in the HI test. No differences were detected in the antibody responses to infective Kunjin virus, within the range 1,400 to 10(9) plaque-forming units (PFU). Below 1,400 PFU, there was no detectable response. Inactivated virus (10(6) PFU) also stimulated the normal antibody response. In contrast, small envelope fragments (derived with 0.2% DOC) and a detergent-solubilized extract of infected cells were unable to stimulate a detectable antibody response and the small envelope fragments may have induced low dose tolerance in one of two rabbits.